Approximately 20-30 percent of infants with severe deficiency of alpha 1-antitrysin develop neonatal hepatitis, usually with progression to cirrhosis. Conversely, at least one-half of infants with clinically- significant neonatal hepatitis have partial or severe deficiency of alpha 1-antitrypsin. A substantial percentage of deficient adults have hepatocellular damage, periportal fibrosis, or frank cirrhosis, as well. In the proposed study, an attempt will be made to develop an animal model for neonatal hepatitis and cirrhosis by the repeated intraperitoneal injection of crystalline papain into rabbits, either alone or concurrent with the administration of other mildly hepatotoxic agents. Preliminary results suggest that such a model is feasible. If so, possible agents for prevention or treatment of individuals at risk will be evaluated in animals similarly treated. Repeated percutaneous liver biopsies will be performed under local anesthesia in test and control rabbits. Biopsies will be evaluated by routine and special light microscopy, electron microscopy, and immunofluorescence. In this way, the progression of lesions in the same rabbits can be followed. Changes in plasma antiproteases and ensymes secondary to papain administration will also be evaluated. The liver changes will be compared with those found in individuals with alpha 1- antitrypsin deficiency, with and without clinically-significant liver disease.